When I made my first fly-collecting expedition to
Africa,
visiting fruit stands and bars in Cameroon to set out fly traps, I
remember that many people seemed quite amused that I had traveled
across the globe to study these seemingly insiginificant creatures.
I can easily understand why. By most human
standards they
are not beautiful, they are not cute and cuddly, and they lack the
majesty of an elephant or a gorilla. Yet they have quite a
following in science, and while I make no attempt to give a full
explanation of their value to biology, I will try to explain why Drosophilamelanogaster is an
ideal study system for my lab's research into the genetic basis of
adaptive evolution.
D. melanogaster became
a leading model organism in population genetics for many of the same
reasons that it has been a mainstay of classical and molecular genetics
for over a century. It's easy to keep in the lab and has a short
generation time, which is obviously helpful for controlled crosses and
lab experiments. Fly stocks can also be inbred, which comes
in
very handy when we want to connect an adaptive phenotype to a causative
locus in the genome. If we can phenotype multiple flies with
the
same homozygous genotype, and focus on mapping the effects of just one
allele per locus instead of two, our job is going to be much easier.
Of course, inbreeding carries caveats that are not always
recognized, especially the exposure of rare deleterious recessive
alleles that would seldom become homozygous in nature, but this can be
overcome by creating "controlled outbred" genotypes from crosses
between pairs of inbred lines.
Population genetics also benefits greatly from the sequencing
of
genomes that are homozygous, as linkage across extended haplotypes
becomes clear. Largely homozygous genomes can be produced
from
inbred lines (Langley
et al.
2012; Mackay
et al.
2012), while fully homozygous genomes from haploid embryos
can be generated by mating females to males carrying a special mutation
(Langley
et al.
2011).D.
melanogaster is
an outcrossing species, and we can study a large number of unrelated
fly stocks collected at the same location and time, which means that
genetic variation corresponds to basic assumptions of population
genetic theory. The species' compact genome (120 Mb) means
that
sequencing a large number of complete genomes from each
population is quite economical, and high sequencing depth produces
consensus genome sequences with very few errors.
The species has undergone noteworthy adaptive
events in
its recent history - first the transition from a wild-living African
species to one essentially dependent on human habitation, and secondly
its worldwide expansion, which has taken it into environments much
different from its sub-Saharan ancestral range (such as Madison,
Wisconsin). Its occupation of diverse environments provides
excellent raw material for the study of local adaptation. For
example, my lab is assembling pairs of population samples that
are geographically close together but come from contrasting altitude
environments. The close relationships these populations share
across most of the genome give us excellent power to detect loci that
differ between populations due to natural selection.
Once we do detect a gene underlying an adaptive
phenotypic
difference between populations, the strongest advantages of D. melanogaster
become apparent. The species' well-annotated genome may help
to
refine our ideas about the specific target of selection.
Even more
significantly, a wide range of molecular, genetic, and
transgenic tools is now at our disposal to reveal the precise mutations
responsible for adaptive evolution and their molecular mechanisms.
A prime example comes from our pigmentation research:
after finding population genetic evidence of selection acting on the regulatory region of the ebony
gene (Pool and Aquadro 2007), I collaborated with Mark Rebeiz and Sean Carroll, who ultimately
used transgenic reporter assays to identify five causative mutations (Rebeiz et al. 2009).
Three of these were in the abdominal enhancer, while the
other two mutations were in a nearby repressor and were
initially
identified based on population genetic evidence.
An important component of the above research's
success in identifying adaptive mutations was
its focus on the genetic basis of adaptation within species, rather
than between distantly related species. In addition to giving
us
evidence for the adaptive nature of the trait (from geographic patterns
of the phenotype, and from genetic variation at a causative locus),
looking within species
meant that few mutations at the causative locus differed between light
and dark individuals, which was critical to efficient identification of
the adaptive mutations. The molecular and transgenic toolkit
showcased by that study, together with the amazing population genomic resources
we now have available, make Drosophila
melanogaster an ideal system for pursuing the genetic basis of adaptive
evolution.